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Nanolipoprotein Particles (NLPs) as an In Vivo Delivery Platform for Biomedical Applications
Author(s) -
Gilmore Sean F.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.06144
Subject(s) - biodistribution , in vivo , immunogenicity , cytotoxicity , chemistry , recombinant dna , nanotechnology , pharmacology , biophysics , in vitro , materials science , biochemistry , biology , immunology , immune system , microbiology and biotechnology , gene
Nanoparticles hold great promise for the delivery of therapeutics. One emerging class of these materials are nanolipoprotein particles (NLPs), which are mimetics of naturally occurring high‐density lipoproteins (HDLs). NLPs are attractive for drug or vaccine formulation since they: (1) can be loaded with hydrophobic “cargo” molecules, (2) have high water solubility and (3) are easily modified for targeted delivery to specific tissues. However, their widespread adoption has been limited by poor in vivo stability, likely due rapid exchange with lipoproteins in blood. We report herein progress towards loading NLPs with several classes of therapeutically relevant molecules and drastic improvement of NLP in vivo stability. Additionally, we have evaluated the functionality, stability, cytotoxicity, toxicity, immunogenicity and in vivo biodistribution of NLPs. We found that a wide range of molecules with disparate chemical properties could be reliably conjugated to NLPs, including proteins, single‐stranded DNA, vaccine adjuvants, and small molecule drugs including chemotherapeutics. We also report an optimized NLP formulation that is highly stable in blood serum, with a half‐life greater than 24 hrs and no cytotoxicity to human cell cultures at doses as high as 320 μg/ml. As NLPs are constructed from lipids and recombinant, truncated apolipoproteins, we report that these particles do not possess any inherent immunogenicity. Biodistribution of the particles is route dependent, but when administered intravenously to mice, we observe uptake into the brain as measured through accelerator mass spectrometry. These findings are supportive of NLPs as a versatile platform that holds promise for use as a delivery vehicle for a range of therapeutics. Support or Funding Information This work was funded by LLNL awards 15‐LW‐023 and 17‐LW‐051.